Real-World Treatment Persistence Among Advanced Therapy-Experienced Patients With Ulcerative Colitis Initiated on Ustekinumab or Adalimumab

Background: Among patients with ulcerative colitis (UC), prior exposure to biologics or advanced therapies is associated with reduced response to future therapies, which may lead to treatment discontinuation. Therapy persistence is a proxy of real-world treatment performance and is important to achieve optimal clinical outcomes. This study compared persistence among advanced therapy-experienced patients with UC initiated on ustekinumab, an anti-interleukin 12/23 antibody, or adalimumab, an anti-tumor necrosis factor biologic. Methods: Adults with UC initiated on ustekinumab or adalimumab (index date) between 10/21/2019 and 03/02/2022 were selected from the IQVIA PharMetrics® Plus database. Patients were advanced therapy-experienced (i.e., had ≥1 claim for a non-index UC-indicated biologic or advanced therapy agent) in the 12-month baseline period before the index date. Patients with other auto-immune diseases during the baseline period were excluded. Cohorts were balanced on baseline characteristics using inverse probability of treatment weights. Persistence was defined as the absence of gaps between days of therapy supply of >120 days for ustekinumab (i.e., twice the 8-week on-label maintenance dosing interval) or >60 days for adalimumab (i.e., twice the mode of days of supply corresponding to 2 doses per the 2-week on-label maintenance dosing interval). Composite endpoints of being persistent while on monotherapy (no immunomodulators, non-index biologics, or advanced therapies) and persistent while corticosteroid-free (< 14 consecutive days of corticosteroid supply after day 90 post-index) were also assessed. All endpoints were evaluated from maintenance phase start until the earlier of 12 months follow-up, end of insurance eligibility or end of data using weighted Kaplan-Meier analyses and weighted Cox proportional hazards models adjusted for the use of ≥2 biologics and class of biologics used during the baseline period. Results: There were 693 patients in the weighted ustekinumab cohort (mean age: 42.6; 45.8% female) and 254 patients in the weighted adalimumab cohort (mean age: 41.6; 46.1% female). At 12 months after the maintenance phase start, 78.1% of the ustekinumab cohort and 59.2% of the adalimumab cohort were persistent on the index biologic; persistence was 2.44 times higher in the ustekinumab cohort relative to the adalimumab cohort (hazard ratio [HR]: 2.44; 95% confidence interval [CI]: 1.82-3.26; p-value: < 0.001). Moreover, 66.7% of the ustekinumab cohort and 40.5% of the adalimumab cohort persisted on the index biologic while on monotherapy; persistence while on monotherapy was 2.53 times higher in the ustekinumab cohort relative to the adalimumab cohort (HR: 2.53; 95% CI: 2.00-3.21; p-value: < 0.001). Finally, 48.0% of the ustekinumab cohort and 42.8% of the adalimumab cohort were persistent while corticosteroid-free; persistence while corticosteroid-free was 1.24 times higher in the ustekinumab cohort relative to the adalimumab cohort (HR: 1.24; 95% CI: 1.01-1.54; p-value 0.0447). Conclusions: Advanced therapy-experienced patients with UC treated with ustekinumab were more persistent, including persistent while on monotherapy and while corticosteroid-free, than patients treated with adalimumab. These findings may aid healthcare providers in choosing a biologic for advanced therapy-experienced patients with UC.